Abstract
Background
To determine whether concurrent chemotherapy is necessary during locoregional radiotherapy (RT) after palliative chemotherapy (PCT) in patients with de novo metastatic nasopharyngeal carcinoma (mNPC).
Methods
A total of 746 patients with mNPC from 2000 to 2017 at our hospital were retrospectively reviewed. Among them, 355 patients received PCT followed by RT. Overall survival (OS) and progression-free survival (PFS), including locoregional progression-free survival (LRPFS) and distant progression-free survival (DPFS) were estimated with the Kaplan–Meier method and log-rank test. Cox proportional-hazards models, landmark analyses, propensity score matching, and subgroup analyses were used to address confounding.
Results
Of the patients included in our study, 192 received radiotherapy alone after PCT (PCT + RT), and 163 received concurrent chemoradiotherapy after PCT (PCT + CCRT). The prognosis of PCT + CCRT was significantly better than that of PCT + RT (5 year OS, 53.0 vs 36.2%; P = 0.004). After matching, the 5 year OS rates of the two groups were 55.7 and 39.0%, respectively (P = 0.034) and the median DPFS were 29.4 and 18.7 months, respectively (P = 0.052). Multivariate Cox regression analysis indicated that PCT + CCRT was an independent favorable prognostic factor (P = 0.009). In addition, conducting concurrent chemoradiotherapy after 4–6 cycles of PCT or conducting concurrent chemotherapy with single-agent platinum was associated with significant survival benefit in the matched cohort (5 year OS rate, 60.4 or 57.4%, respectively). The survival difference between groups remained significant when evaluating patients who survived for ≥ 1 year (P = 0.028).
Conclusions
The optimal treatment strategy of mNPC is the combination of PCT followed by concurrent chemoradiotherapy. More specifically, concurrent chemoradiotherapy with single-agent platinum after 4–6 cycles of PCT is suggested.
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Background
Nasopharyngeal carcinoma (NPC) is a malignant tumor of the nasopharyngeal epithelium that exhibits an unbalanced geographical distribution [1]. In endemic regions, especially in South China, the worldwide age-standardized incidence rate of NPC is up to 25.39/100 000 person-years [2]. Among them, 4–10% of patients present with de novo metastatic nasopharyngeal carcinoma (mNPC), and the 5-year survival rate of mNPC is approximately 20% [3, 4]. According to the current National Comprehensive Cancer Network (NCCN) guidelines, platinum-based palliative chemotherapy (PCT) with or without locoregional radiotherapy (RT) is the cornerstone of treatment for patients with mNPC [5]. Many retrospective studies have asserted that cycles of PCT are not always positively related to survival and 4–6 cycles are recommended [31]. A phase I clinical trial of 27 patients with recurrent or metastatic NPC suggested that pembrolizumab treatment resulted in a median OS of 16.5 months. [32] Another phase II trial of nivolumab also suggested the potential use of immunotherapy for mNPC as the median OS of 44 patients receiving nivolumab was 17.1 months. [33] In addition to monotherapy, a phase I clinical trial from China demonstrated that the therapeutic effect of camrelizumab combined with chemotherapy was superior to that of camrelizumab alone [34]. The superior efficacy of the camrelizumab combination was recently confirmed in a phase III randomized study [35]. Therefore, how to use immunotherapy in addition to chemotherapy and radiotherapy to maximize the survival of patients with mNPC is worth further effort.
Our study had several limitations that should be mentioned. The source of patients who underwent PCT followed by RT was restricted to one hospital, and the sample size was not sufficiently large. As this study was retrospective in nature, selection bias and imbalances existed. Plasma EBV testing results were not available, although EBV was an important factor for therapeutic monitoring and prognostic evaluations. In addition, quality of life, late toxicity and some details on the following lines of therapy were not considered in this study. Thus, prospective studies are warranted to support our findings.
Conclusions
The real-world study suggests that concurrent chemoradiotherapy significantly improves OS compared with radiotherapy alone after palliative chemotherapy in patients with de novo metastatic nasopharyngeal carcinoma. More specifically, concurrent chemoradiotherapy with single-agent platinum after 4–6 cycles of chemotherapy can be considered.
Availability of data and materials
The authenticity of this article has been validated by uploading the key raw data onto the Research Data Deposit public platform (www.researchdata.org.cn). All data will be shared upon request to the corresponding author.
Abbreviations
- NPC:
-
Nasopharyngeal carcinoma
- mNPC:
-
De novo metastatic nasopharyngeal carcinoma
- NCCN:
-
National Comprehensive Cancer Network
- PCT:
-
Palliative chemotherapy
- RT:
-
Radiotherapy
- OS:
-
Overall survival
- CCRT:
-
Concurrent chemoradiotherapy
- HR:
-
Hazard ratio
- WHO:
-
World Health Organization
- PF:
-
Cisplatin plus 5-fluorouracil
- TP:
-
Cisplatin plus docetaxel
- TPF:
-
Cisplatin plus docetaxel plus 5-fluorouracil
- IMRT:
-
Intensity-modulated radiotherapy
- CR:
-
Complete response
- PR:
-
Partial response
- SD:
-
Stable disease
- PD:
-
Progressive disease
- PFS:
-
Progression-free survival
- LRPFS:
-
Locoregional progression-free survival
- DPFS:
-
Distant progression-free survival
- PSM:
-
Propensity score matching
- CI:
-
Confidence interval
- KPS:
-
Karnofsky performance score
- EBV:
-
Epstein-Barr virus
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Funding
This work was supported by the National Key R & D Program of Precise Medical Research of China (NO. 2016YFC0904600), the National Natural Science Foundation of China (No. 81872464), and the Natural Science Foundation of Guangdong Province (No. 2018A030310236).
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Conception and design: SHZ, YTW and YFX; Administrative support: SRL, CC and YFX; Provision of study materials or patients: SRL and YFX; Collection and assembly of data: SHZ, YTW, ZLH, GNW, JTLand SRD; Data analysis and interpretation: SHZ, CC and YFX; Manuscript writing: All authors. All authors read and approved the final manuscript.
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The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). The study was approved by ethics board of Sun Yat-sen University Cancer Center and individual consent for this retrospective analysis was waived.
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Supplementary Information
Additional file 1: Description of the radiotherapy. Figure S1.
Patient selection diagram. Figure S2. Overall Survival (OS) for patients treated with chemoradiotherapy (CRT) or palliative chemotherapy (PCT) in de novo metastatic nasopharyngeal carcinoma. Table S1. Details of common chemotherapy regimens. Table S2. Summary of studies related to locoregional radiotherapy in de novo metastatic nasopharyngeal carcinoma. Table S3. Adverse effects. References.
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Zheng, SH., Wang, YT., Liu, SR. et al. Addition of chemoradiotherapy to palliative chemotherapy in de novo metastatic nasopharyngeal carcinoma: a real-world study. Cancer Cell Int 22, 36 (2022). https://doi.org/10.1186/s12935-022-02464-7
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DOI: https://doi.org/10.1186/s12935-022-02464-7